Abstract Immune checkpoint inhibitor (ICI) immunotherapeutics are having an important and expanding impact on the treatment of cancer. After only a few years of clinical use, ICIs have become a multi-billion dollar family of products. However, only ~30% of patients have a positive response to treatment. To date, the best indicator for a positive response is the microsatellite instability (MSI) status. Individuals, no matter what the cancer type, that are MSI-High have as high as 80% positive response rate. However, to date only cancers with a high frequency of MSI-H, e.g. colon cancer, are routinely screened for MSI status. However, the high positive response rate of MSI-H patients has led to the urging that all cancers be screened for MSI status. Roche and Merck have just announced plans to develop a test to do so. They will pursue one of the two standard assays, immunohistochemistry (IHC), in which tumor sections are stained for presence of 4 proteins involved in mis- match repair. The other is PCR of 6 long MSs to determine if there is an insertion or deletion of a base. We propose a fundamentally different strategy. Since the determining immunological outcome of MSI is the production of frameshift peptides, we will measure the patient's immune reactivity against all 220,000 possible tumor produced FS peptides (FSP) using a propriety peptide microarray containing all possible FSPs. This simple assay uses a small volume of blood as opposed to a tumor biopsy, and by measuring the antibodies produced against the FS peptides, provides a rapid, accurate scoring of MSI status. This would afford the possibility of inexpensively and simply determining the MSI status for all cancer patients from a small amount of blood.